Variant chr10-132208050-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_173575.4(STK32C):c.1421C>T(p.Pro474Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000259 in 1,158,792 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 35)

Exomes 𝑓: 0.0000026 ( 0 hom. )

Consequence

STK32C
NM_173575.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0850

Variant links:

Genes affected

STK32C (HGNC:21332): (serine/threonine kinase 32C) The protein encoded by this gene is a member of the serine/threonine protein kinase family. It is thought that this family member is functional in brain due to its high expression levels there. DNA methylation differences have been found in this gene in monozygotic twins that are discordant for adolescent depression. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2016]

STK32C links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.109268695).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
STK32C	NM_173575.4 link	c.1421C>T	p.Pro474Leu	missense_variant	12/12	ENST00000298630.8	NP_775846.2	Q86UX6-1A0A140VJW0B7Z7J1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
STK32C	ENST00000298630.8 link	c.1421C>T	p.Pro474Leu	missense_variant	12/12	1	NM_173575.4	ENSP00000298630.3	Q86UX6-1
STK32C	ENST00000368622.5 link	c.1070C>T	p.Pro357Leu	missense_variant	12/12	1		ENSP00000357611.1	Q86UX6-2
STK32C	ENST00000462160.5 link	n.1308C>T		non_coding_transcript_exon_variant	13/13	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000259

AC:

AN:

1158792

Hom.:

Cov.:

AF XY:

0.00000180

AC XY:

AN XY:

555228

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000314

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 12, 2024

The c.1421C>T (p.P474L) alteration is located in exon 12 (coding exon 12) of the STK32C gene. This alteration results from a C to T substitution at nucleotide position 1421, causing the proline (P) at amino acid position 474 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.064

BayesDel_noAF

Benign

-0.33

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0089

.;T

Eigen

Benign

-0.46

Eigen_PC

Benign

-0.40

FATHMM_MKL

Benign

0.64

LIST_S2

Benign

0.78

T;T

M_CAP

Benign

0.036

MetaRNN

Benign

0.11

T;T

MetaSVM

Benign

-0.83

MutationAssessor

Benign

1.6

.;L

PrimateAI

Uncertain

0.57

PROVEAN

Benign

-1.6

N;N

REVEL

Benign

0.055

Sift

Uncertain

0.019

D;D

Sift4G

Uncertain

0.059

T;T

Polyphen

0.56

P;B

Vest4

0.11

MVP

0.71

MPC

0.25

ClinPred

0.18

GERP RS

2.5

Varity_R

0.067

gMVP

0.20

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over